We have developed a recombinant polypeptide that we have termed Fc-Dimers (Di-mers). This product has potent anti-inflammatory activity in vitro, and we propose to test this reagent in an animal model of autoimmune disease. We have selected the murine disease, Experimental Autoimmune Encephalomyelitis (EAE), a model for human multiple sclerosis (MS). Pathology in this disease correlates with the migration of activated macrophages into nervous tissue and the consequent destruction of nerve conduction resulting in paralysis. We propose to induce EAE in mice using well- established protocols, and then determine whether the administration of Fc-Dimers can reduce, delay, or reverse the symptoms associated with this autoimmune disease. This application addresses a disease in which inflammatory cytokines play a major role. We have developed a therapeutic that reverses inflammatory cytokine production by macrophages, and therefore may be effective in treating this disease. In this Phase I STTR application we have established a collaborative arrangement in which LeukoSight will produce, purify, and test the Fc-Dimers in vitro and provide them to the university research laboratory. The university research laboratory will test the effectiveness of Fc-Dimers in reversing pathology associated with EAE. The university research laboratory has proficiency in this disease model and in the immunological analysis of immune cell infiltration into the CNS. The University has provided IACUC approval to perform these studies. In collaboration with the University of Maryland, LeukoSight will determine the dose of Fc-Dimers needed to reverse disease and then examine the mechanisms by which Fc-Dimers reverse autoimmune disease. The goal of these studies is to demonstrate (for the first time) that a therapeutic directed at reprogramming macrophages has the potential to treat autoimmune diseases. PUBLIC HEALTH RELEVANCE: We have developed polypeptides consisting of fragments of IgG which have potent anti- inflammatory activity. The goal of this application is to determine the degree to which Fc-Dimers can delay or reverse the autoimmune pathology associated with EAE, an animal model for human multiple sclerosis.